CN103087063A - Preparation method of moxifloxacin and salts of moxifloxacin - Google Patents
Preparation method of moxifloxacin and salts of moxifloxacin Download PDFInfo
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Abstract
The invention discloses a preparation method of moxifloxacin and salts of moxifloxacin. The preparation method comprises the following steps of: preparing the intermediate 1-cyclopropyl-6,7- difluoro-8-methoxyl-4-1,4-dihydro-3-quinoline carboxylic acid trialkyl tin complex of moxifloxacin and salts of moxifloxacin by reaction between 1-cyclopropyl-6,7- difluoro-8- methoxyl-4-oxo-1,4-dihydro-3-quinoline carboxylic acid and trialkyl stannic chloride, then, preparing the moxifloxacin by coupled reaction between the intermediate and the S, S-2, 8- dinitrogen diazo bicyclic [4.3.0] nonyl hydride, and further obtaining the moxifloxacin hydrochloride (as FORMULA I) by salification with hydrochloric acid and devitrification with absolute ethyl alcohol. The preparation method provided by the invention is simple and convenient in process operation steps, and is low in cost; the product moxifloxacin hydrochloride prepared by the method is high in purity and yield; and the preparation method is suitable for industrial mass production.
Description
Technical field
The invention belongs to the pharmaceutical chemistry technical field, be specifically related to the preparation method of a kind of Moxifloxacin and salt thereof.
Background technology
Moxifloxacin hydrochloride be the 4th generation the wide spectrum fluoroquinolone antibacterial agent, chemistry 1-cyclopropyl-7-(S by name, S-2,8-diazabicyclo [4.3.0] nonane-8-yl)-6-fluoro-8-methoxy-4-oxo-1,4-dihydro-3-quinoline carboxylic acid hydrochloride, developed by Bayer A.G, in September, 1999 is in German Initial Public Offering, examine by FDA December in the same year, go on the market in the U.S., its English name is: Moxifloxacin hydrochloride, chemical structural formula be suc as formula shown in I, CAS:186826-86-8.
The more classical synthetic method of Moxifloxacin hydrochloride mainly contains following a few class at present:
CN102190657 adopts magnesium salts and 1-cyclopropyl-6, after 7-two fluoro-Isosorbide-5-Nitrae-dihydros-8-methoxyl group-4-oxo-3-quinolinic acid or its ester formation complex compound, then carries out linked reaction with (4as, 7as)-octahydro-1H-pyrroles [3,4-b] pyridine and prepares Moxifloxacin.
US5157117, WO2008059223A2, CN10973992 and CN101514201 disclose and have utilized 1-cyclopropyl-6,7-two fluoro-1,4-dihydro-8-methoxyl group-4-oxo-3-quinolinic acid (or its ester) forms the borine inner complex with boric acid and propionic anhydride (or diacetyl oxide) reaction, then under the condition of organic bases again with (4as, 7as)-octahydro-1H-pyrroles [3,4-b] the pyridine reaction, prepare Moxifloxacin hydrochloride finally by salt-forming reaction.
EP1992626 discloses 1-cyclopropyl-6,7-two fluoro-Isosorbide-5-Nitrae-dihydros-8-methoxyl group-4-oxo-3-quinolinic acid and S, and S-2,8-diazabicyclo [4.3.0] nonane is take DMF and DMSO as solvent, at about 70 ℃ reaction 6～8h, preparation Moxifloxacin; Use again L (+)-tartrate or fumaric acid that it is split, obtain purer Moxifloxacin.
EP550903 discloses and has utilized 1-cyclopropyl-6,7-two fluoro-1,4-dihydro-8-methoxyl group-4-oxo-3-quinolinic acid and S, S-2,8-diazabicyclo [4.3.0] nonane carries out linked reaction and prepares Moxifloxacin, due to 1-cyclopropyl-6,7-two fluoro-1,6 of 4-dihydro-8-methoxyl group-4-oxo-3-quinolinic acid and 7 selectivity low, cause containing in products obtained therefrom 6 digit pairs connection impurity, need remove through silicagel column again.
There is complex process in above-mentioned several synthetic method, and cost is high, the shortcoming that yield is low, and the part public technology also needs to carry out the purifying of chiral separation or silicagel column, is difficult to realize large-scale industrial production.
Summary of the invention
For above-mentioned the deficiencies in the prior art, the object of the present invention is to provide that a kind of technological operation step is easy, production cost is low, and products obtained therefrom purity and the high Moxifloxacin of yield and the preparation method of salt thereof.
For achieving the above object, the present invention takes following measure:
at first the preparation method of Moxifloxacin of the present invention and salt thereof adopts 1-cyclopropyl-6, 7-difluoro-8-methoxyl-4-oxo-1, Moxifloxacin and salt intermediate 1-cyclopropyl-6 thereof are made in 4-dihydro-3-quinoline carboxylic acid and the reaction of trialkyl tin chloride, 7-difluoro-8-methoxyl-4-oxo-1, 4-dihydro-3-quinoline carboxylic acid trialkylated tin complex compound (formula II), then with S, S-2, 8-diazabicyclo [4.3.0] nonane (formula III) carries out linked reaction and prepares Moxifloxacin (formula IV), again by hydrochloric acid salify and dehydrated alcohol crystallization, convert Moxifloxacin to Moxifloxacin hydrochloride (formula I), preparation flow is as shown in flow process 1.
Flow process 1
Particularly, the preparation method of Moxifloxacin of the present invention and salt thereof comprises the steps:
(1) preparation of Moxifloxacin and salt intermediate thereof
In organic solvent, when temperature is 80～140 ℃, with 1-cyclopropyl-6,7-difluoro-8-methoxyl-4-oxo-1,4-dihydro-3-quinoline carboxylic acid and trialkyl tin chloride react, and the reaction times is 1～10h, get intermediate 1-cyclopropyl-6,7-difluoro-8-methoxyl-4-oxo-Isosorbide-5-Nitrae-dihydro-3-quinoline carboxylic acid trialkylated tin complex compound (formula II) reaction solution; Wherein, described organic solvent is dimethylbenzene, toluene, acetonitrile or tetrahydrofuran (THF); Described trialkyl tin chloride is trimethyltin chloride, triisopropyl tin chloride, fentin chloride or tributyltin chloride;
(2) preparation of Moxifloxacin and salt thereof
Intermediate (formula II) reaction solution and S that step (1) is prepared, S-2,8-diazabicyclo [4.3.0] nonane mixes, at 40～100 ℃ of lower insulation reaction 3～6h, be cooled to 40～60 ℃, add the hydrochloric acid of 4～6mol/l, vigorous stirring 1～2h, filter, standing separatory gets respectively organic layer and hydrochloric acid water layer; Organic layer is reclaimed respectively to get reactive material organic solvent and the trialkyl tin chloride in step (1) by underpressure distillation; The hydrochloric acid water layer is evaporated to 150～250ml, adds dehydrated alcohol, 0～5 ℃ of lower stirring and crystallizing 1～3h filters and obtains Moxifloxacin hydrochloride (formula I).
In the preparation method of above-mentioned Moxifloxacin and salt thereof, 1-cyclopropyl-6 in described step (1), the mol ratio of 7-difluoro-8-methoxyl-4-oxo-Isosorbide-5-Nitrae-dihydro-3-quinoline carboxylic acid and trialkyl tin chloride is 1: 1～6.
In the preparation method of above-mentioned Moxifloxacin and salt thereof, 1-cyclopropyl-6 in described step (1), 7-difluoro-8-methoxyl-4-oxo-Isosorbide-5-Nitrae-dihydro-mole number of 3-quinoline carboxylic acid and the volume ratio of organic solvent are 1mmol: 2～8ml.
In the preparation method of above-mentioned Moxifloxacin and salt thereof, S in 1-cyclopropyl-6 in described step (1), 7-difluoro-8-methoxyl-4-oxo-Isosorbide-5-Nitrae-dihydro-3-quinoline carboxylic acid and step (2), S-2, the mol ratio of 8-diazabicyclo [4.3.0] nonane is 1: 1～4.
In the preparation method of above-mentioned Moxifloxacin and salt thereof, S in described step (2), S-2,8-diazabicyclo [4.3.0] nonane mole: hydrochloric acid volume: dehydrated alcohol volume=1mmol: 2～4ml: 0.5～3ml.
The present invention compared with prior art has following advantage:
(1) the inventive method first adopts 1-cyclopropyl-6, 7-difluoro-8-methoxyl-4-oxo-1, Moxifloxacin and salt intermediate 1-cyclopropyl-6 thereof are made in 4-dihydro-3-quinoline carboxylic acid and the reaction of trialkyl tin chloride, 7-difluoro-8-methoxyl-4-oxo-1, 4-dihydro-3-quinoline carboxylic acid trialkylated tin complex compound, again with S, S-2, 8-diazabicyclo [4.3.0] nonane carries out linked reaction and prepares Moxifloxacin, can effectively avoid because 6 digit pairs join (1-cyclopropyl-6, 7-difluoro-8-methoxyl-4-oxo-1, 4-dihydro-3-quinoline carboxylic acid's 6 and S, S-2, 8-diazabicyclo [4.3.0] nonane generation coupling) impurity that produces, simplified follow-up purification step, products obtained therefrom purity is higher.
(2) the inventive method trialkyl tin chloride used can be realized recycling by simple acid treatment and underpressure distillation, and the rate of recovery is high, can reach more than 95%, greatly reduces the raw materials cost of the inventive method.
(3) technological operation step of the present invention is easy, and the yield of products obtained therefrom Moxifloxacin hydrochloride is higher, its molar yield approximately 90%.
Embodiment
Below in conjunction with embodiment, summary of the invention of the present invention is described in further detail.Should understand, embodiments of the invention only are used for explanation the present invention and unrestricted the present invention, in the situation that do not break away from the technology of the present invention thought, and according to ordinary skill knowledge and customary means, various replacements and the change made all should comprise within the scope of the invention.
Embodiment 1
In being housed, the 1000ml reaction flask of mechanical stirring, reflux and thermometer adds 1-cyclopropyl-6,7-difluoro-8-methoxyl-4-oxo-1,4-dihydro-3-quinoline carboxylic acid 230mmol and trimethyltin chloride 240mmol and 500ml dimethylbenzene, be warming up to 90 ℃, stirring reaction 10h, cool to again 40～45 ℃, get intermediate (formula I) reaction solution, stand-by.
The stand-by intermediate reaction liquid that takes a morsel is dissolved in deuterochloroform with the gained intermediate and carries out the nuclear-magnetism structural identification after the decompression precipitation.
1H?NMR(400MHz，CDCl
3)：δ=8.70(s，1H)，6.81（m，1H），4.15(m，1H)，3.84(s，3H)，1.35(m，2H)，1.10(m，2H)，0.71(s，9H)；
13C?NMR(75MHz，CDCl
3)：δ=176.5，171.5，150.7，146.7，139.2，134.6，130.4，130.0，109.2，107.3，55.7，35.9，7.6，0.2。
The stand-by intermediate reaction liquid that takes a morsel carries out the LC-MS coupling, [M+H]
+Observed value: 459.22; The intermediate molecular formula is: C
17H
19F
2NO
4Sn, molecular weight: 458.04.
Embodiment 2
In being housed, the 1000ml reaction flask of mechanical stirring, reflux and thermometer adds 1-cyclopropyl-6,7-difluoro-8-methoxyl-4-oxo-1,4-dihydro-3-quinoline carboxylic acid 200mmol and triisopropyl tin chloride 400mmol and 600ml toluene, be warming up to 120 ℃, stirring reaction 8h, cool to again 40～45 ℃, get intermediate (formula I) reaction solution, stand-by.
The stand-by intermediate reaction liquid that takes a morsel is dissolved in deuterochloroform with the gained intermediate and carries out the nuclear-magnetism structural identification after the decompression precipitation.
1H?NMR(400MHz，CDCl
3)：δ=8.71(s，1H)，6.83（m，1H），4.14(m，1H)，3.83(s，3H)，1.65(m，3H)，1.31(m，2H)，1.11(m，2H)，0.91(d，18H)；
13C?NMR(75MHz，CDCl
3)：δ=176.6，171.8，151.0，146.9，139.5，135.1，130.6，130.3，109.3，107.6，55.9，36.3，19.6，11.8，7.7。
The stand-by intermediate reaction liquid that takes a morsel carries out the LC-MS coupling, [M+H]
+Observed value: 543.31; The intermediate molecular formula is: C
23H
31F
2NO
4Sn, molecular weight: 542.20.
Embodiment 3
In being housed, the 1000ml reaction flask of mechanical stirring, reflux and thermometer adds 1-cyclopropyl-6,7-difluoro-8-methoxyl-4-oxo-1,4-dihydro-3-quinoline carboxylic acid 150mmol and fentin chloride 600mmol and 700ml acetonitrile, be warming up to 110 ℃, stirring reaction 6h, cool to 40～45 ℃, get intermediate (formula I) reaction solution, stand-by.
The stand-by intermediate reaction liquid that takes a morsel is dissolved in deuterochloroform with the gained intermediate and carries out the nuclear-magnetism structural identification after the decompression precipitation.
1H?NMR(400MHz，CDCl
3)：δ=8.69(s，1H)，7.30-7.51（m，15H），6.81(t，1H)，4.15(m，1H)，3.85(s，3H)，1.36(m，2H)，1.12(m，2H)；
13C?NMR(75MHz，CDCl
3)：δ=176.6，171.5，150.9，146.7，139.9，135.2，134.8，134.1，132.3，130.4，129.8，108.8，107.0，55.3，35.8，7.4。
The stand-by intermediate reaction liquid that takes a morsel carries out the LC-MS coupling, [M+H]
+Observed value: 645.33; The intermediate molecular formula is: C
32H
25F
2NO
4Sn, molecular weight: 644.25.
Embodiment 4
In being housed, the 1000ml reaction flask of mechanical stirring, reflux and thermometer adds 1-cyclopropyl-6,7-difluoro-8-methoxyl-4-oxo-1,4-dihydro-3-quinoline carboxylic acid 100mmol and tributyltin chloride 500mmol and 600ml tetrahydrofuran (THF), be warming up to 80 ℃, stirring reaction 3h, cool to again 40～45 ℃, get intermediate (formula I) reaction solution, stand-by.
The stand-by intermediate reaction liquid that takes a morsel is dissolved in deuterochloroform with the gained intermediate and carries out the nuclear-magnetism structural identification after the decompression precipitation.
1H?NMR(400MHz，CDCl
3)：δ=8.73(s，1H)，6.84（m，1H），4.14(m，1H)，3.84(s，3H)，1.55-1.64(m，12H)，1.30(m，6H)，1.05-1.34(m，4H)，0.91(t，9H)；
13C?NMR(75MHz，CDCl
3)：δ=176.7，171.9，151.3，147.2，139.6，135.3，130.8，130.5，109.7，107.6，56.1，36.5，28.8，27.3，20.7，13.9，7.9。
The stand-by intermediate reaction liquid that takes a morsel carries out the LC-MS coupling, [M+H]
+Observed value: 585.32; The intermediate molecular formula is: C
26H
37F
2NO
4Sn, molecular weight: 584.28.
Embodiment 5
In being housed, the 1000ml reaction flask of mechanical stirring, reflux and thermometer adds 1-cyclopropyl-6,7-difluoro-8-methoxyl-4-oxo-1,4-dihydro-3-quinoline carboxylic acid 90mmol and fentin chloride 540mmol and 650ml dimethylbenzene, be warming up to 140 ℃, stirring reaction 1h, cool to again 40～45 ℃, get intermediate (formula I) reaction solution, stand-by.
The stand-by intermediate reaction liquid that takes a morsel carries out the LC-MS coupling, [M+H]
+Observed value: 645.19; The intermediate molecular formula is: C
32H
25F
2NO
4Sn, molecular weight: 644.25.
Embodiment 6
In being housed, the 2000ml reaction flask of mechanical stirring, reflux and thermometer adds the prepared intermediate of embodiment 1 (formula I) reaction solution, stir, add S, S-2,8-diazabicyclo [4.3.0] nonane 460mmol finishes, and is warmed up to 60 ℃, insulation reaction, HPLC monitoring (instrument is Shimadzu LC-20A) reacts completely through 5h; Be cooled to 40～60 ℃, add 4～6mol/L hydrochloric acid 1400ml, vigorous stirring 1～2h removes by filter a small amount of insolubles impurity, and standing separatory is collected respectively dimethylbenzene organic layer and hydrochloric acid water layer;
Organic layer reclaims respectively dimethylbenzene and trimethyltin chloride by underpressure distillation, and wherein the rate of recovery of trimethyltin chloride is 95.7%, but the regenerant direct circulation is applied mechanically preparation intermediate (formula I);
The hydrochloric acid water layer is evaporated to 150～200ml, adds the 950ml dehydrated alcohol, and 0～5 ℃ of lower stirring and crystallizing 1～3h filters and obtains Moxifloxacin hydrochloride (formula II) product, HPLC purity 99.3%, yield 88.4%.
Embodiment 7
In being housed, the 2000ml reaction flask of mechanical stirring, reflux and thermometer adds the prepared intermediate of embodiment 2 (formula I) reaction solution, stir, add S, S-2,8-diazabicyclo [4.3.0] nonane 800mmol finishes, and is warmed up to 40 ℃, insulation reaction, the HPLC monitoring reacts completely through 6h; Be cooled to 40～60 ℃, add 4～6mol/L hydrochloric acid 3200ml, vigorous stirring 1～2h removes by filter a small amount of insolubles impurity, and standing separatory is collected respectively toluene organic layer and hydrochloric acid water layer;
Organic layer reclaims respectively toluene and triisopropyl tin chloride by underpressure distillation, and wherein the triisopropyl tin chloride rate of recovery is 96.3%, but the regenerant direct circulation is applied mechanically preparation intermediate of the present invention (formula I);
The hydrochloric acid water layer is evaporated to 150～200ml, adds the 2400ml dehydrated alcohol, and 0～5 ℃ of lower stirring and crystallizing 1～3h filters and obtains Moxifloxacin hydrochloride (formula II) product, HPLC purity 99.1%, yield 92.0%.
Embodiment 8
In being housed, the 2000ml reaction flask of mechanical stirring, reflux and thermometer adds the prepared intermediate of embodiment 3 (formula I) reaction solution, stir, add S, S-2,8-diazabicyclo [4.3.0] nonane 450mmol finishes, and is warmed up to 80 ℃, insulation reaction, the HPLC monitoring reacts completely through 4.5h; Be cooled to 40～60 ℃, add 4～6mol/L hydrochloric acid 900ml, vigorous stirring 1～2h removes by filter a small amount of insolubles impurity, and standing separatory is collected respectively acetonitrile organic layer and hydrochloric acid water layer;
Organic layer reclaims respectively acetonitrile and fentin chloride by underpressure distillation, and wherein the rate of recovery of fentin chloride is 97.4%, but the regenerant direct circulation is applied mechanically preparation intermediate of the present invention (formula I);
The hydrochloric acid water layer is evaporated to 150～200ml, adds the 600ml dehydrated alcohol, and 0～5 ℃ of lower stirring and crystallizing 1～3h filters and obtains Moxifloxacin hydrochloride (formula II) product, HPLC purity 99.5%, yield 92.1%.
Embodiment 9
In being housed, the 2000ml reaction flask of mechanical stirring, reflux and thermometer adds the prepared intermediate of embodiment 4 (formula I) reaction solution, stir, add S, S-2,8-diazabicyclo [4.3.0] nonane 100mmol finishes, and is warmed up to 100 ℃, insulation reaction, the HPLC monitoring reacts completely through 3h; Be cooled to 40～60 ℃, add 4～6mol/L hydrochloric acid 200ml, vigorous stirring 1～2h removes by filter a small amount of insolubles impurity, and standing separatory is collected respectively tetrahydrofuran (THF) organic layer and hydrochloric acid water layer;
Organic layer reclaims respectively tetrahydrofuran (THF) and tributyltin chloride by underpressure distillation, and wherein the rate of recovery of tributyltin chloride is 98.0%, but the regenerant direct circulation is applied mechanically preparation intermediate of the present invention (formula I);
The hydrochloric acid water layer is evaporated to 150～200ml, adds the 100ml dehydrated alcohol, and 0～5 ℃ of lower stirring and crystallizing 1～3h filters and obtains Moxifloxacin hydrochloride (formula II) product, HPLC purity 99.2%, yield 89.0%.
Embodiment 10
In being housed, the 2000ml reaction flask of mechanical stirring, reflux and thermometer adds the prepared intermediate of embodiment 5 (formula I) reaction solution, stir, add S, S-2,8-diazabicyclo [4.3.0] nonane 90mmol finishes, and is warmed up to 100 ℃, insulation reaction, the HPLC monitoring reacts completely through 3.5h; Be cooled to 40～60 ℃, add 4～6mol/L hydrochloric acid 180ml, vigorous stirring 1～2h removes by filter a small amount of insolubles impurity, and standing separatory is collected respectively dimethylbenzene organic layer and hydrochloric acid water layer;
Organic layer reclaims respectively dimethylbenzene and fentin chloride by underpressure distillation, and wherein the rate of recovery of fentin chloride is 98.5%, but the regenerant direct circulation is applied mechanically preparation intermediate of the present invention (formula I); The hydrochloric acid water layer is evaporated to 150～200ml, adds the 45ml dehydrated alcohol, and 0～5 ℃ of lower stirring and crystallizing 1～3h filters and obtains Moxifloxacin hydrochloride (formula II) product, HPLC purity 99.7%, yield 91.9%.
Claims (5)
1. the preparation method of a Moxifloxacin and salt thereof, is characterized in that, comprises the steps:
(1) preparation of Moxifloxacin and salt intermediate thereof
In organic solvent, when temperature is 80～140 ℃, with 1-cyclopropyl-6,7-difluoro-8-methoxyl-4-oxo-1,4-dihydro-3-quinoline carboxylic acid and trialkyl tin chloride react, and the reaction times is 1～10h, get the intermediate 1-cyclopropyl-6 of formula II, 7-difluoro-8-methoxyl-4-oxo-Isosorbide-5-Nitrae-dihydro-3-quinoline carboxylic acid trialkylated tin complex compound reaction solution; Wherein, described organic solvent is dimethylbenzene, toluene, acetonitrile or tetrahydrofuran (THF); Described trialkyl tin chloride is trimethyltin chloride, triisopropyl tin chloride, fentin chloride or tributyltin chloride
(2) preparation of Moxifloxacin and salt thereof
The intermediate 1-cyclopropyl-6 that step (1) is prepared, 7-difluoro-8-methoxyl-4-oxo-Isosorbide-5-Nitrae-dihydro-3-quinoline carboxylic acid trialkylated tin complex compound reaction solution and S, S-2,8-diazabicyclo [4.3.0] nonane mixes, at 40～100 ℃ of lower insulation reaction 3～6h, be cooled to 40～60 ℃, add the hydrochloric acid of 4～6mol/l, vigorous stirring 1～2h, filter, standing separatory gets respectively organic layer and hydrochloric acid water layer; Organic layer is reclaimed respectively to get reactive material organic solvent and the trialkyl tin chloride in step (1) by underpressure distillation; The hydrochloric acid water layer is evaporated to 150～250ml, adds dehydrated alcohol, 0～5 ℃ of lower stirring and crystallizing 1～3h filters and obtains the Moxifloxacin hydrochloride shown in formula I
2. the preparation method of Moxifloxacin according to claim 1 and salt thereof is characterized in that: 1-cyclopropyl-6 in described step (1), the mol ratio of 7-difluoro-8-methoxyl-4-oxo-Isosorbide-5-Nitrae-dihydro-3-quinoline carboxylic acid and trialkyl tin chloride is 1: 1～6.
3. the preparation method of Moxifloxacin according to claim 1 and salt thereof, it is characterized in that: 1-cyclopropyl-6 in described step (1), 7-difluoro-8-methoxyl-4-oxo-Isosorbide-5-Nitrae-dihydro-mole number of 3-quinoline carboxylic acid and the volume ratio of organic solvent are 1mmol: 2～8ml.
4. the preparation method of Moxifloxacin according to claim 1 and salt thereof, it is characterized in that: 1-cyclopropyl-6 in described step (1), 7-difluoro-8-methoxyl-4-oxo-1, S in 4-dihydro-3-quinoline carboxylic acid and step (2), S-2, the mol ratio of 8-diazabicyclo [4.3.0] nonane is 1: 1～4.
5. the preparation method of Moxifloxacin according to claim 1 and salt thereof is characterized in that: S in described step (2), S-2,8-diazabicyclo [4.3.0] nonane mole: hydrochloric acid volume: dehydrated alcohol volume=1mmol: 2～4ml: 0.5～3ml.
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| CN105669671A (en) * | 2016-03-10 | 2016-06-15 | 陈红 | Preparation method of moxifloxacin hydrochloride |
| CN105524060B (en) * | 2016-03-10 | 2017-03-22 | 青岛云天生物技术有限公司 | Method for preparing moxifloxacin hydrochloride |
| CN114249722A (en) * | 2020-09-23 | 2022-03-29 | 常州方圆制药有限公司 | Preparation method of moxifloxacin hydrochloride |
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